Primary prevention

Teplizumab, a humanized monoclonal antibody targeting the T-cell surface marker CD3, is the only therapy that has, to date, been approved for use in delaying progression from stage 2 (autoimmunity and dysglycemia in the prediabetic range) to stage 3; clinical type 1 diabetes.​[48]​ Teplizumab has been approved by the US Food and Drug Administration (FDA) and is recommended by the American Diabetes Association (ADA) to delay the onset of stage 3 type 1 diabetes in people 8 years of age and older with stage 2 type 1 diabetes.[1]​ Management should be in a specialized setting with appropriately trained personnel.[1]

In a phase 2, randomized, placebo-controlled trial of 76 people with stage 2 type 1 diabetes who had relatives with established type 1 diabetes, the median time to onset of clinical type 1 diabetes was delayed by about 2.7 years in the teplizumab group compared with the placebo group.[60]​ Challenges with teplizumab use include its limited indication for stage 2 type 1 diabetes (i.e., few people are currently being identified), high cost, and logistical difficulties with its administration.[48]​ The Pediatric Endocrine Society has published a statement providing an overview of considerations for the use of teplizumab in clinical practice.[61]

Teplizumab is also being investigated as a potential disease-modifying drug in new onset stage 3 type 1 diabetes. It has been shown to be associated with lower insulin use and higher area under the curve (AUC) of C-peptide (indicating greater overall C-peptide secretion) in patients with early type 1 diabetes.[62][63][64][65] However, in one meta-analysis, teplizumab was found to impart higher risks of grade 3 or higher adverse events, adverse events leading to discontinuation, nausea, rash, and lymphopenia.[65]​ Trials with other drugs targeting 1) autoimmune responses, 2) antigen presentation, 3) glycemic dysregulation, and 4) beta-cell stress/dysfunction are underway.[48]

Secondary prevention

Prevention of cardiovascular disease (CVD)

  • CVD is the major cause of death and a major cause of morbidity for patients with diabetes. It is the leading cause of hospital admission among patients with diabetes, with ischemic/coronary heart disease as the predominant subtype.​[242]

  • Intensive glycemic control has been shown to decrease the incidence of macrovascular disease in type 1 diabetes.[229]​ During the 30-year follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, high doses of insulin were associated with a less favorable cardiometabolic risk profile (higher body mass index, pulse rate, triglycerides, lower high-density lipoprotein [HDL] cholesterol), but intensive control continued to have long-term beneficial effects on the incidence of cardiovascular disease in type 1 diabetes.​​​​[230]​​​​[243]

  • CVD risk can be further decreased by modification of other cardiovascular risk factors (e.g., hypertension, dyslipidemia, and smoking), which should be assessed at least once a year in all patients.[1][244]​​ Lifestyle and behavioral therapy are essential components of treatment. All patients should have smoking-cessation counseling and treatment as needed. See Diabetic cardiovascular disease.

Retinopathy screening

  • In adults, initial screening for retinopathy by an ophthalmologist or optometrist is recommended within 5 years of initial diagnosis of diabetes, and every 1-2 years thereafter if there is no evidence of retinopathy (and glycemic goals are met).​[1] In the presence of abnormal findings (and in the presence of risk factors such as uncontrolled hyperglycemia), more frequent follow-up is indicated as appropriate (e.g., at least annually).​[1]

  • In children, an initial dilated and comprehensive eye exam is recommended once they have had type 1 diabetes for 3-5 years, provided they are ages ≥11 years or puberty has started, whichever is earlier.[1] The examination should then be repeated every 2 years.[1] Less frequent examinations, every 4 years, may be acceptable on the advice of an eye care professional and based on risk factor assessment, including a history of HbA1c <8% (<64 mmol/mol).[1]

Immunizations

  • Patients should be up to date with their vaccination schedule, with vaccines provided in accordance with age-specific guidelines for the general population.​​​​​​​​ Specific recommendations for patients with diabetes in particular are as follows:[1]

    • Annual influenza immunizations for all individuals ≥6 months of age; people with diabetes are cautioned against taking the live attenuated influenza vaccine (which is delivered by nasal spray) and are instead recommended to receive the inactive or recombinant influenza vaccination.

    • Vaccination against pneumococcal disease; there are two types of vaccines available in the US, the pneumococcal conjugate vaccines (PCV13, PCV15, PCV20, and PCV21) and the pneumococcal polysaccharide vaccine (PPSV23), with distinct schedules for children and adults.

    • Vaccination against COVID-19 for all people ≥6 months of age; patients with type 1 diabetes are at higher risk for severe COVID-19 infection. They are more likely to need hospitalization, intensive care, and mechanical ventilation compared with patients who do not have diabetes, and have a higher case fatality rate and increased odds of in-hospital death with COVID-19.​​​[293][294][295][296] Poor glycemic control, hypertension, recent diabetic ketoacidosis, previous stroke, previous heart failure, renal impairment, body mass index <20 kg/m² or ≥40 kg/m², male sex, older age, nonwhite ethnicity, and socioeconomic deprivation are associated with increased mortality from COVID-19.[296][297][298]​ See Coronavirus disease 2019 (COVID-19).

    • Single-dose vaccination against respiratory syncytial virus (RSV) for adults ages ≥60 years with insulin-treated diabetes.

    • Hepatitis B vaccination for unvaccinated adults with diabetes ages 19-59 years; considered for unvaccinated adults with diabetes ages 60 years and older.

Bone health​

  • The ADA advises that older adults should be assessed for fracture risk as part of their routine diabetes care, according to risk factors and comorbidities.​[1] In addition to general risk factors, diabetes-specific risk factors for fracture include frequent hypoglycemic events, diabetes duration >10 years, use of insulin, HbA1c >8%, and presence of microvascular complications.[1]​ A dual-energy X-ray absorptiometry (DEXA) scan every 2-3 years is recommended by the ADA for older adults (ages >65 years) and younger people with multiple risk factors.[1] Those with low bone mineral density (T-score ≤-2.0) or with previous fragility fractures should be considered for bone protection agents (e.g., antiresorptive or osteoanabolic drugs).[1] Steps should be taken to reduce the risk of falls, including individualizing glycemic goals for those at elevated fracture risk and avoiding hypoglycemia.[1]

  • Regular bone densitometry in children and adolescents is not recommended by the International Society for Pediatric and Adolescent Diabetes, but individualized evaluation of bone health may be considered in specific populations (e.g., those with coexisting celiac disease, or family history of early osteoporosis).​[48]

  • It is important that people with diabetes (including children) have adequate calcium and vitamin D intake, either through diet alone or with supplementation, and that other bone health promoting behaviors are encouraged (e.g., avoiding smoking, regular weight-bearing exercise).[1] Screening for vitamin D deficiency should be considered, especially in high-risk groups and those with darker skin tone.[48]

Dental care

  • Periodontal disease is more severe, and may be more prevalent, in people with diabetes than in those without and has been associated with higher HbA1c levels. People with diabetes should be referred for a dental exam at least once per year.[1] The ADA recommends that dental health professionals should be included in the diabetes care team, and that early detection of oral health problems by clinicians may be helpful to promote prompt referral to dental care and mitigate the expensive and extensive procedures needed to treat advanced oral disease.[1] Clinical assessment of people with diabetes should include a dental history, and dental professionals should be informed about key aspects of the person’s health and diabetes treatment plan, including glycemic goals, drugs, and comorbid conditions. It is important for dental professionals to know when people with diabetes have high HbA1c levels, as this population may have lower oral healing capacity.[1]

  • Patients with insulin-treated diabetes are vulnerable to hypoglycemia during dental procedures, especially if fasting. Ensuring their safety requires close coordination between dental professionals and the diabetes care team.[1] Preprocedure planning, including potential drug adjustments and blood glucose monitoring, is essential for hypoglycemia prevention. Dental offices should be equipped with the necessary tools, such as blood glucose monitors, carbohydrates, and glucagon, to promptly address any hypoglycemic episodes.[1]

Cancer-screening

  • The ADA advises that, given the association between diabetes and an increased risk of various cancers, people should be encouraged to attend recommended age- and sex-appropriate cancer screenings to facilitate earlier detection and treatment, and to reduce modifiable risk factors such as obesity, physical inactivity and smoking.[1]

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